The purpose of this investigation is to further elucidate the strcture and control of biosynthesis of IgA, the major class of immunoglobulins of the secretory fluids. With immunologic methods we have recently identified two subclasses of rabbit IgA ("f" and "g" subclasses); two or more allotypes (genetic variants) of each subclass are known. Available data indicate that the "f" subclass of secretory IgA (sIgA) is resistant to cleavage by papain in the absence of cysteine, whereas the "g" subclass of sIgA is cleaved into Fc2 alpha and Fab2 alpha fragments. We propose to determine the structural basis for a) subclass differences, b) allotypic differences and c) the differential sensitivity of sIgA to proteolytic digestion. A combination of immunologic and biochemical methods will be used to separate the subclasses and to study: a) light chain-heavy chain bonding, b) secretory component interactions with IgA (i.e., covalent versus non-covalent bonding), and c) cysteine-containing tryptic peptides. We propose to localize further the allotypic markers of sIgA by developing methods to cleave the "f" subclass of IgA and by preparing and characterizing peptic and tryptic fragments of the "g" subclass of IgA. Allotypic markers will be used in studies relating to control of biosynthesis of IgA. We propose to determine the effects of various antibody reagents on the phenotypic expression (immunologic suppression) of various IgA molecules and to identify the genes controlling biosynthesis of IgA.